Analysis of matrix metalloproteinases in cancer cell signaling and extracellular behavior

Despite the fact that over the past two decades the total death rate has declined up to twenty percent, cancer remains the second leading cause of death in the United States and accounts for nearly one in every four deaths. It is therefore of paramount importance that new strategies continue to develop in an effort to curb both incidence and treatment of disease. The current research landscape is focused on developing strategies to disrupt molecular signatures of cancer cell types, commonly known as targeted therapy. Of particular importance in the advancement of targeted therapies are matrix metalloproteinases (MMPs), a family of endopeptidases whose primary function lies in cleaving extracellular matrix (ECM) proteins and are frequently dysregulated in cancer. While research regarding MMPs is decades old, their significance in the signal transduction of several oncogenic pathways is yet to be fully explored. In addition, a dearth of quantitative data exists describing the action of MMPs in three dimensional (3D) networks, a configuration that causes cells to express vastly different behaviors compared to traditional two-dimensional (2D) in vitro culture methods. This dissertation aims to further elucidate the intimate relationships between MMPs, the ECM, cancer pathway signaling, and cell migration. First, the behavioral crosstalk between MMPs and the ECM is studied using quantitative methods in 3D matrices. Next, the role of MMPs in both Ras oncogenic and HER2 positive breast cancer is probed via extensive protein expression analysis. Finally, the behavioral aspects of MMPs in 3D are assessed marrying both in vitro data with a computational model to predict migration response. The results reveal that MMPs exhibit a bidirectional relationship with respect to matrix architecture, and the ability to regulate and be regulated by the ECM. In addition, it is concluded that MMPs play a significant role in both active Ras and HER2 upregulated cancer signaling. Finally, the data demonstrates the robustness and accuracy of our methods in manufacturing a model to predict migration in 3D matrices. The work described here promises to further enhance the knowledge of MMPs in cancer and potentially inform future drug development endeavors

Self-Positioning Smart Buoys, The \u27Un-Buoy\u27 Solution: Logistic Considerations Using Autonomous Surface Craft Technology and Improved Communications Infrastructure

Moored buoys have long served national interests, but incur high development, construction, installation, and maintenance costs. Buoys which drift off-location can pose hazards to mariners, and in coastal waters may cause environmental damage. Moreover, retrieval, repair and replacement of drifting buoys may be delayed when data would be most useful. Such gaps in coastal buoy data can pose a threat to national security by reducing maritime domain awareness. The concept of self-positioning buoys has been advanced to reduce installation cost by eliminating mooring hardware. We here describe technology for operation of reduced cost self-positioning buoys which can be used in coastal or oceanic waters. The ASC SCOUT model is based on a self-propelled, GPS-positioned, autonomous surface craft that can be pre-programmed, autonomous, or directed in real time. Each vessel can communicate wirelessly with deployment vessels and other similar buoys directly or via satellite. Engineering options for short or longer term power requirements are considered, in addition to future options for improved energy delivery systems. Methods of reducing buoy drift and position-maintaining energy requirements for self-locating buoys are also discussed, based on the potential of incorporating traditional maritime solutions to these problems. We here include discussion of the advanced Delay Tolerant Networking (DTN) communications draft protocol which offers improved wireless communication capabilities underwater, to adjacent vessels, and to satellites. DTN is particularly adapted for noisy or loss-prone environments, thus it improves reliability. In addition to existing buoy communication via commercial satellites, a growing network of small satellites known as PICOSATs can be readily adapted to provide low-cost communications nodes for buoys. Coordination with planned vessel Automated Identification Systems (AIS) and International Maritime Organization standards for buoy and vessel notificat- - ion systems are reviewed and the legal framework for deployment of autonomous surface vessels is considered

Equivalence Properties by Typing in Cryptographic Branching Protocols

International audienceRecently, many tools have been proposed for automatically analysing, in symbolic models, equivalence of security protocols. Equivalence is a property needed to state privacy properties or game-based properties like strong secrecy. Tools for a bounded number of sessions can decide equivalence but typically suffer from efficiency issues. Tools for an unbounded number of sessions like Tamarin or ProVerif prove a stronger notion of equivalence (diff-equivalence) that does not properly handle protocols with else branches. Building upon a recent approach, we propose a type system for reasoning about branching protocols and dynamic keys. We prove our type system to entail equivalence , for all the standard primitives. Our type system has been implemented and shows a significant speedup compared to the tools for a bounded number of sessions, and compares similarly to ProVerif for an unbounded number of sessions. Moreover, we can also prove security of protocols that require a mix of bounded and unbounded number of sessions, which ProVerif cannot properly handle

Land Use and West Nile Virus Seroprevalence in Wild Mammals

We examined West Nile virus (WNV) seroprevalence in wild mammals along a forest-to-urban gradient in the US mid-Atlantic region. WNV antibody prevalence increased with age, urbanization, and date of capture for juveniles and varied significantly between species. These findings suggest several requirements for using mammals as indicators of transmission

Detection by Enzyme-Linked Immunosorbent Assay of Antibodies to West Nile virus in Birds

We adapted an indirect immunoglobulin G enzyme-linked immunosorbent assay to facilitate studies of West Nile virus (WNV) and evaluated its application to taxonomically diverse avian species. Anti-WNV antibodies were detected in 23 bird species, including many exotic species, demonstrating its value in studies of WNV epizootiology

Climatological predictions of the auroral zone locations driven by moderate and severe space weather events

Auroral zones are regions where, in an average sense, aurorae due to solar activity are most likely spotted. Their shape and, similarly, the geographical locations most vulnerable to extreme space weather events (which we term ‘danger zones’) are modulated by Earth’s time-dependent internal magnetic field whose structure changes on yearly to decadal timescales. Strategies for mitigating ground-based space weather impacts over the next few decades can benefit from accurate forecasts of this evolution. Existing auroral zone forecasts use simplified assumptions of geomagnetic field variations. By harnessing the capability of modern geomagnetic field forecasts based on the dynamics of Earth’s core we estimate the evolution of the auroral zones and of the danger zones over the next 50 years. Our results predict that space-weather related risk will not change significantly in Europe, Australia and New Zealand. Mid-to-high latitude cities such as Edinburgh, Copenhagen and Dunedin will remain in high-risk regions. However, northward change of the auroral and danger zones over North America will likely cause urban centres such as Edmonton and Labrador City to be exposed by 2070 to the potential impact of severe solar activity

Less is more: Antibiotics at the beginning of life.

Antibiotic exposure at the beginning of life can lead to increased antimicrobial resistance and perturbations of the developing microbiome. Early-life microbiome disruption increases the risks of developing chronic diseases later in life. Fear of missing evolving neonatal sepsis is the key driver for antibiotic overtreatment early in life. Bias (a systemic deviation towards overtreatment) and noise (a random scatter) affect the decision-making process. In this perspective, we advocate for a factual approach quantifying the burden of treatment in relation to the burden of disease balancing antimicrobial stewardship and effective sepsis management

West Nile Virus, Venezuela

Submitted by Sandra Infurna ([email protected]) on 2020-04-01T17:32:07Z No. of bitstreams: 1 AnthonyE_Guimaraes_etal_IOC_2007.pdf: 108341 bytes, checksum: db1489aeeb51b9f823abd6e1273378ef (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2020-04-01T17:51:00Z (GMT) No. of bitstreams: 1 AnthonyE_Guimaraes_etal_IOC_2007.pdf: 108341 bytes, checksum: db1489aeeb51b9f823abd6e1273378ef (MD5)Made available in DSpace on 2020-04-01T17:51:00Z (GMT). No. of bitstreams: 1 AnthonyE_Guimaraes_etal_IOC_2007.pdf: 108341 bytes, checksum: db1489aeeb51b9f823abd6e1273378ef (MD5) Previous issue date: 2007University of Massachusetts Medical School. Center for Infectious Disease and Vaccine Research. Worcester, MA, USA.Universidad de Carabobo Biomed. Maracay, Venezuela.Universidad Central de Venezuela. Caracas, Venezuela.Coleccion Ornitologica Phelps. Caracas, Venezuela.New York State Department of Health. Albany, New York, USA / State University of New York at Albany. Albany, New York, USA.New York State Department of Health. Albany, New York, USA / State University of New York at Albany. Albany, New York, USA.New York State Department of Health. Albany, New York, USA / State University of New York at Albany. Albany, New York, USA.Universidad Central de Venezuela. Maracay, Venezuela.Instituto Nacional de Investigaciones Agrícolas. Maracay, Venezuela.Universidad Central de Venezuela, Caracas, VenezuelaFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Centers for Disease Control and Prevention. San Juan, Puerto Rico, USA.Universidad del Zulia. Maracaibo, Venezuela.Universidad de Carabobo Biomed. Maracay, Venezuela.Ministerio de Salud Insalud. Carabobo, Venezuela.Universidad Central de Venezuela, Caracas, VenezuelaUniversidad de Carabobo Biomed. Maracay, Venezuela.Centers for Disease Control and Prevention.Fort Collins, Colorado, USA.Harvard School of Public Health. Boston, Massachusetts, USA.New York State Department of Health. Albany, New York, USA / State University of New York at Albany. Albany, New York, USA

Molecular Epidemiology of Eastern Equine Encephalitis Virus, New York

Southern strains are undergoing amplification, perpetuation, and overwintering in New York

Analysis of Antibiotic Exposure and Early-Onset Neonatal Sepsis in Europe, North America, and Australia.

IMPORTANCE Appropriate use of antibiotics is life-saving in neonatal early-onset sepsis (EOS), but overuse of antibiotics is associated with antimicrobial resistance and long-term adverse outcomes. Large international studies quantifying early-life antibiotic exposure along with EOS incidence are needed to provide a basis for future interventions aimed at safely reducing neonatal antibiotic exposure. OBJECTIVE To compare early postnatal exposure to antibiotics, incidence of EOS, and mortality among different networks in high-income countries. DESIGN, SETTING, AND PARTICIPANTS This is a retrospective, cross-sectional study of late-preterm and full-term neonates born between January 1, 2014, and December 31, 2018, in 13 hospital-based or population-based networks from 11 countries in Europe and North America and Australia. The study included all infants born alive at a gestational age greater than or equal to 34 weeks in the participating networks. Data were analyzed from October 2021 to March 2022. EXPOSURES Exposure to antibiotics started in the first postnatal week. MAIN OUTCOMES AND MEASURES The main outcomes were the proportion of late-preterm and full-term neonates receiving intravenous antibiotics, the duration of antibiotic treatment, the incidence of culture-proven EOS, and all-cause and EOS-associated mortality. RESULTS A total of 757 979 late-preterm and full-term neonates were born in the participating networks during the study period; 21 703 neonates (2.86%; 95% CI, 2.83%-2.90%), including 12 886 boys (59.4%) with a median (IQR) gestational age of 39 (36-40) weeks and median (IQR) birth weight of 3250 (2750-3750) g, received intravenous antibiotics during the first postnatal week. The proportion of neonates started on antibiotics ranged from 1.18% to 12.45% among networks. The median (IQR) duration of treatment was 9 (7-14) days for neonates with EOS and 4 (3-6) days for those without EOS. This led to an antibiotic exposure of 135 days per 1000 live births (range across networks, 54-491 days per 1000 live births). The incidence of EOS was 0.49 cases per 1000 live births (range, 0.18-1.45 cases per 1000 live births). EOS-associated mortality was 3.20% (12 of 375 neonates; range, 0.00%-12.00%). For each case of EOS, 58 neonates were started on antibiotics and 273 antibiotic days were administered. CONCLUSIONS AND RELEVANCE The findings of this study suggest that antibiotic exposure during the first postnatal week is disproportionate compared with the burden of EOS and that there are wide (up to 9-fold) variations internationally. This study defined a set of indicators reporting on both dimensions to facilitate benchmarking and future interventions aimed at safely reducing antibiotic exposure in early life